The human skin is a complex three-dimensional tissue comprised of an outer layer, the epidermis, with an underlying connective tissue layer, the dermis which contains numerous cell types including fibroblasts, endothelial cells and immune populations. The cutaneous vasculature is a dynamic system that regulates blood flow and will rapidly proliferate to generate a de novo vascular network in response to injury, tissue growth or hypoxia. In recent years, advances in single cell genomics and computational methods have facilitated a revolution in the ability to analyse transcriptional profiles at the single cell level. As part of the Human Cell Atlas project – an international collaborative effort to map all cell types within the human body – single cell RNA sequencing (scRNAseq) has been performed on in excess of a hundred thousand cells from the dermis derived from healthy individuals using the chromium 10X platform. Analysis of this dataset reveals subpopulations of vascular endothelial cells, lymphatic endothelial cells and pericytes. To understand how cellular identify is dictated by the interplay of intrinsic factors and spatial localisation within the tissue we have integrated in vivo dynamic optical computed tomography skin imaging with confocal and lightsheet microscopy and RNAscope. We are studying the relative contributions of tissue context and intrinsic transcriptional programs to vascular cell identity. In future work, we will apply these methods to understand perturbations in vascular cell biology in disease states including psoriasis, skin cancer and rosacea.

Three-dimensional models of human skin at single-cell resolution in health and disease